Impact of Escaped Bone Marrow Mesenchymal Stromal Cells on Extracardiac Organs after Intramyocardial Implantation in a Rat Myocardial Infarction Model

Abstract

Cell escape occurs after intramyocardial injection for treatment of myocardial infarction (MI) and then the migrated cells might be entrapped by extracardiac organs. We investigated the fate of migrated bone marrow-derived mesenchymal stromal cells (MSCs) and their impact on lung, liver, and spleen. MI model was created by coronary artery ligation in female Lewis rats. Three weeks after the ligation, bromodeoxyuridine (BrdU)-labeled male MSCs were directly injected into the infarcted area in the cell transplantation group ( n = 22). The same volume of phosphate-buffered solution (PBS) was injected in the control group ( n = 21). In the sham group ( n = 10) intramyocardial injection of the same volume of PBS was performed in healthy rats. Four weeks later, echocardiography was performed and the cell retention was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry study was performed to identify the migrated cells. Heart function was improved after the cell injection. qRT-PCR results showed the percentage of retained cells in heart, spleen, liver, and lung ranked 3.63 ± 0.48%, 0.77 ± 0.13%, 0.68 ± 0.10%, 0.62 ± 0.11%, respectively, after cell transplantation. The implanted MSCs that escaped to liver, spleen, and lung did not differentiate into fibroblast, myofibroblast, or alveolar epithelial cells. However, the migrated MSCs in liver expressed functional hepatocyte marker. In conclusion, cell migration after intramyocardial injection did not result in deterioration of lung, liver, and spleen function. Our study might pave the way for new safety investigation of emerging cell resources and their impact on target and untargeted organs.